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Acute Myeloid Leukemia (AML) Treatment Regimens Clinical Trials: The National Comprehensive Cancer Network recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. uInduction Therapy1 Note: All recommendations are Category 2A unless otherwise indicated. The NCCN believes the best option for any patient with cancer is in a clinical trial and strongly encourages this option for all patients. PATIENT CRITERIA REGIMEN AND DOSING Age <60 years2-8 Days 1–3: An anthracycline (daunorubicin 60–90mg/m2 IV OR idarubicin 12mg/m2) Days 1–7: Cytarabine 100–200mg/m2 continuous IV (Category 1). OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV Days 1–5: Cladribine 5 mg/m2. OR Days 1–3: An anthracycline (daunorubicin 60mg/m2 IV OR idarubicin 12mg/m2 for 1 cycle) Days 1–6: High-dose cytarabine 2g/m2 IV every 12 hours OR Days 1–4: High-dose cytarabine 3g/m2 IV every 12 hours (Category 1 for patients ≤45 years, category 2B for other age groups). OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV every 12 hours Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1, 3, 5: Dual-drug liposomal encapsulation of cytarabine 100mg/m2 + daunorubicin 44mg/m2 IV over 90 minutes (Category 2B).b OR Days 1, 4, 7: Daunorubicin 60mg/m2 + gemtuzumab ozogamicin 3mg/m2 (up to one 4.5 mg vial) Days 1–7: Cytarabine 200mg/m2 continuous IV OR Days 1–7: SC granulocyte-colony stimulating factor (G-CSF) Days 2–6: Fludarabine 30mg/m2 plus high-dose cytarabine 2g/m2 over 4 hours after starting fludarabine on days 2–6 Days 4–6: Idarubicin 8mg/m2 IV (Category 2B). Age ≥60 years6-10 Days 1–3: An anthracycline (daunorubicin 60–90mg/m2 IV OR idarubicin 12mg/m2 IV OR mitoxantrone 12mg/m2 IV) De novo AML without unfavorable Days 1–7: Cytarabine 100–200mg/m2 continuous IV. cytogenetics or molecular OR markers; no antecedent Days 1–3: Daunorubicin 60mg/m2 IV hematologic disorder; and no Days 1–7: Cytarabine 200mg/m2 continuous IV therapy-related AML Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1, 4, 7: Daunorubicin 60mg/m2 + gemtuzumab ozogamicin 3mg/m2 (up to one 4.5 mg vial) Days 1–7: Cytarabine 200mg/m2 continuous IV (for CD33-positive AML). Age ≥60 years6,7,9,10 Lower-intensity therapy Unfavorable cytogenetics or Days 1–7: 5-azacytidine 75mg/m2 IV every 28 days molecular markers; antecedent OR hematologic disorder; therapy- Days 1–5: Decitabine 20mg/m2 IV for a 4-week cycle. related AML OR Days 1–3: An anthracycline (daunorubicin 60–90mg/m2 IV OR idarubicin 12mg/m2 IV OR mitoxantrone 12mg/m2 IV) Days 1–7: Cytarabine 100–200mg/m2 continuous IV. OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1, 3, 5: Dual-drug liposomal encapsulation of cytarabine 100mg/m2 + daunorubicin 44mg/m2 IV over 90 minutes (Category 1).b Clofarabine-based regimens (Category 3). continued 1 CancerTherapyAdvisor.com Acute Myeloid Leukemia (AML) Treatment Regimens uInduction Therapy1 (continued) PATIENT CRITERIA REGIMEN AND DOSING Age ≥60 years11-15 Lower-intensity therapy Not a candidate for intensive Days 1–10: Cytarabine 20mg SC twice daily. therapy or declines intensive OR therapy Days 1–7: 5-azacytidine 75mg/m2 IV every 28 days (preferred). OR Days 1–5: Decitabine 20mg/m2 IV every 28 days (preferred). OR Day 1: Gemtuzumab ozogamicin 6mg/m2 IV Day 8: Gemtuzumab ozogamicin 3mg/m2 IV (CD-33 positive). OR Enasidenib 100mg orally once daily (IDH-2 mutated AML). OR Best supportive care (hydroxyurea, transfusion support). uPost-Remission Therapy1 Age <60 years12,13 Days 1, 3, and 5: High-dose cytarabine 3g/m2 IV over 3 hours every 12 hours for 3–4 cycles (Category 1) Core binding factor cytogenetic OR translocations without KIT Days 1–3: High-dose cytarabine 3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. mutation or favorable-risk OR molecular abnormalities Days 1–4: Cytarabine 1g/m2 every 12 hours Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to 4.5mg vial) for 2 cycles Day 1 (Cycle 1) or Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV (For CD33-positive AML). Age <60 years Matched sibling or alternative donor HCT. Intermediate-risk and/or OR molecular abnormalities Days 1, 3, 5, OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. OR Days 1, 3, 5, OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1–4: Cytarabine 1g/m2 every 12 hours Day 1 (Cycle 1) or Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to one 4.5mg vial) for 2 cycles (for CD33-positive AML). Age <60 years Matched sibling or alternative donor HCT. Treatment-related disease other OR than CBF and/or poor-risk Days 1, 3, and 5 OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. cytogenetics and/or molecular OR abnormalities Days 1, 3, and 5 OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours. Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1 and 3: Dual-drug liposomal encapsulation of cytarabine 65mg/m2 + daunorubicin 29mg/m2 IV over 90 minutes (Category 2B).b Age ≥60 years Reduced-intensity HCT. Complete Response After OR Previous Intensive Therapy Cytarabine 100–200mg/m2 IV for 5–7 days for 1–2 cycles ± anthracycline (idarubicin or daunorubicin). OR Cytarabine 1–1.5g/m2 IV for 4–6 doses for 1–2 cycles for patients with good performance status, normal renal function, better-risk or normal karyotype with favorable molecular markers. OR Days 1, 3, and 5: Cytarabine 1–1.5g/m2 over 3 hours every 12 hours Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1 and 3: Dual-drug liposomal encapsulation of cytarabine 65mg/m2 + daunorubicin 29mg/m2 IV over 90 minutes.b OR Days 1–4: Cytarabine 1000mg/m2 IV every 12 hours Day 1 (Cycle 1) OR Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to one 4.5mg vial) for 2 cycles (for CD33-positive AML). OR Maintenance therapy with hypomethylating regimen (5-azacytidine, decitabine) every 4–6 weeks until progression. OR Observation. continued 2 CancerTherapyAdvisor.com Acute Myeloid Leukemia (AML) Treatment Regimens uPost-Remission Therapy1 (continued) PATIENT CRITERIA REGIMEN AND DOSING Age ≥60 years Allogeneic HCT (preferably in clinical trial). Induction Failure After Previous OR Intensive Therapy Best supportive care. Age ≥60 years Reduced-intensity HCT. Response After Previous Lower OR Intensity Therapy Continue hypomethylating regimens (5-azacytidine, decitabine) every 4–6 weeks until progression. OR Day 1: Gemtuzumab ozogamicin 2mg/m2 every 4 weeks up to 8 continuation courses (CD33-positive AML). OR Continue enasidenib until progression (IDH-2 mutated AML). Age ≥60 years Best supportive care. No Response or Progression After Previous Lower Intensity Therapy uTherapy for Relapse or Refractory Disease1 Age <60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Early Relapse (<12 months) Age <60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Late Relapse (≥12 months) OR Repeat initial successful induction regimen. Age ≥60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Early Relapse (<12 months) OR Best supportive care. Age ≥60 years Repeat initial successful induction regimen. Late Relapse (≥12 months) OR Chemotherapy* followed by matched sibling or alternative donor HCT. OR Best supportive care. *Chemotherapy Aggressive therapy for appropriate patients: Options8-10, 14-19, 23, 24 Days 1–5: Cladribine 5mg/m2 IV Days 1–5: Cytarabine 2g/m2 IV Days 0–5: G-CSF 300mcg SC, ± Days 1–3: Mitoxantrone 10mg/m2 IV OR idarubicin 10mg/m2 IV. OR High-dose cytarabine (if not previously used in treatment) ± anthracycline. OR Days 1–5: Fludarabine 30mg/m2 IV over 0.5 hours Days 1–5: Cytarabine 2g/m2 IV over 4 hours Days 0 to polymorphonuclear recovery (>0.5 x 109/L): G-CSF 5mcg/kg or 300mcg/m2 (G-CSF may also start on Day +6 until engraftment) ± Days 1–3: Idarubicin 10mg/m2 IV.
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  • LEUKEMIA CHEMOTHERAPY REGIMENS (Part 1 of 2) the Selection, Dosing, and Administration of Anti-Cancer Agents and the Management of Associated Toxicities Are Complex

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    LEUKEMIA CHEMOTHERAPY REGIMENS (Part 1 of 2) The selection, dosing, and administration of anti-cancer agents and the management of associated toxicities are complex. Drug dose modifications and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and because of individual patient variability, prior treatment, and comorbidities. Thus, the optimal delivery of anti-cancer agents requires a healthcare delivery team experienced in the use of such agents and the management of associated toxicities in patients with cancer. The chemotherapy regimens below may include both FDA-approved and unapproved uses/regimens and are provided as references only to the latest treatment strategies. Clinicians must choose and verify treatment options based on the individual patient. REGIMEN DOSING Acute Myeloid Leukemia (AML) Induction Therapy Cytarabine (Cytosar-U; ARA-C) + Days 1–3: An anthracycline (eg, daunorubicin at least 60mg/m2/day IV, an anthracycline idarubicin 10–12mg/m2/day IV, or mitoxantrone 10–12mg/m2/day IV), plus (daunorubicin [Cerubidine], Days 1–7: Cytarabine 100–200mg/m2/day continuous IV infusion. idarubicin [Idamycin], OR mitoxantrone [Novantrone])1, 2 Days 1–3: An anthracycline (eg, daunorubicin 45mg/m2/day IV, idarubicin 12mg/m2/day IV, or mitoxantrone 12mg/m2/day IV), plus Days 1–7: Cytarabine 100mg/m2/day continuous IV infusion. Intermediate-dose cytarabine3 Cycle 1 Days 1–7: Cytarabine 200mg/m2/day continuous IV infusion, plus Days 5–6: Idarubicin 12mg/m2/day IV. Cycle 2 Days 1–6: Cytarabine 1,000mg/m2 continuous IV infusion for 3 hrs twice daily, plus Days 3, 5 and 7: Amsacrine 120mg/m2/day.